WO2022252404A1 - Fluorosulfonyl free radical reagent, and preparation method therefor and use thereof - Google Patents

Abstract

Provided in the present invention are a fluorosulfonyl free radical reagent, and a preparation method therefor and the use thereof, belonging to the technical field of organic synthesis. The fluorosulfonyl free radical reagent provided by the present invention can efficiently generate fluorosulfonyl free radicals and results in a corresponding free radical reaction, and the product yield is high. Moreover, the fluorosulfonyl free radical reagent provided by the present invention is applicable to an extremely wide range of substrates, and can be reacted with various types of olefin substrates and alkyne substrates to efficiently synthesize fluorosulfonylation products. Furthermore, the fluorosulfonyl free radical reagent provided by the present invention is in a stable solid state at room temperature, is non-volatile, low in toxicity, easy to store and convenient to use, and has important academic and application values. In addition, the present invention provides a preparation method for the fluorosulfonyl free radical reagent. The preparation method is easy to operate and suitable for large-scale production.

Description

A kind of fluorosulfonyl free radical reagent and its preparation method and application

This application claims the priority of the Chinese patent application submitted to the China Patent Office on May 31, 2021, with the application number CN202110597989.9, and the invention title "a fluorosulfonyl radical reagent and its preparation method and application". The entire contents are incorporated by reference in this application.

technical field

The invention relates to the technical field of organic synthesis, in particular to a fluorosulfonyl free radical reagent and its preparation method and application.

Background technique

Since Professor K.Barry Sharpless and Jiajia Dong (Angew.Chem.Int.Ed.2014,53,9430) first proposed and successfully realized the hexavalent sulfur-fluorine exchange reaction in 2014, this type of reaction has been used in organic synthesis chemistry, Materials chemistry, medicinal chemistry, and chemical biology, especially the selective labeling and modification of protein molecules, have received widespread attention and shown good application prospects. It is called a new generation of click chemistry, which has triggered a new era in current fluorine chemistry research. hotspots.

Sulfonyl fluoride compounds, as the most important class of compounds containing hexavalent sulfur-fluorine bonds, have attracted extensive attention from materials, chemistry and biologists. In the existing research, the fluorine-chlorine exchange reaction is an important method for the synthesis of sulfonyl fluoride compounds, but this method has limited its wide application due to the lack of stability, applicability and substrate source limitations (Angew.Chem.Int . Ed. 2014, 53, 9430). As an ideal nucleophilic acceptor, alkenylsulfonyl fluoride can obtain sulfonyl fluoride products through nucleophilic addition, free radical addition or Diels-Alder reaction (J.Org.Chem.1979,44,3847; Angew. Chem.Int.Ed.2009,48,9879; Nat.Commun.2019,10,3752), but the structure of the sulfonyl fluoride product obtained by this method is relatively simple. In addition, there are more commercial reagents such as sulfuryl fluoride gas (SO ₂ F ₂ ), and solid sulfonyl fluoride reagents such as FDIT and AISF are widely used in the synthesis of sulfonyl fluoride compounds as "FSO ₂ ⁺ " synthons (Angew. Chem. Int. Ed. 2014, 53, 9430; Angew. Chem. Int. Ed. 2018, 57, 2605; Org. Lett. 2018, 20, 812). Although the above reagents can be used in the synthesis of sulfonyl fluoride compounds, there are still few studies on the use of fluorosulfonyl radical reagents in the synthesis of sulfonyl fluoride compounds through the free radical route.

In 2020, Professor Liao Saihu's research group used sulfonyl fluoride chloride (FSO ₂ Cl) as a fluorosulfonyl radical reagent for the first time to catalyze the generation of fluorosulfonyl radicals under visible light conditions and the fluorosulfonylation of alkenes (Angew.Chem . Int. Ed. 2021, 60, 3956-3960). However, FSO ₂ Cl is used as a fluorosulfonyl radical reagent, and the substrate applicability and yield of some products need to be improved; especially, FSO ₂ Cl exists in gaseous form under normal temperature and pressure conditions, and is volatile and highly toxic. Its storage and transportation and applications have many limitations.

Contents of the invention

The object of the present invention is to provide a fluorosulfonyl free radical reagent and its preparation method and application. The fluorosulfonyl free radical reagent provided by the present invention can efficiently generate fluorosulfonyl free radicals and undergo corresponding free radical reactions. The product yield High; at the same time, the fluorosulfonyl free radical reagent provided by the invention is in a stable solid state at room temperature, non-volatile, low toxicity, easy to store, and convenient to use.

In order to achieve the above-mentioned purpose of the invention, the present invention provides the following technical solutions:

The present invention provides a fluorosulfonyl radical reagent, including a cation and an anion, and the cation has a structure shown in formula I-1 or formula I-2:

The R ¹ and R ² are independently hydrogen or an alkyl group, R ³ is an alkyl group, Ar ¹ and Ar ² are independently an aromatic ring or a substituted aromatic ring;

The anion is

^- BF ₄ , ^- BF ₆ , ^- PF ₆ , ^- PF ₄ , ^- SbF ₆ , ^- NTf ₂ or ^- AsF ₆ .

Preferably, the aromatic ring is a benzene ring, a naphthalene ring, an anthracene ring or a phenanthrene ring, and the substituent in the substituted aromatic ring is an alkyl group or an electron-deficient group.

Preferably, the electron deficient group includes -F, -Cl, -Br, trifluoromethyl, nitrile, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl or alkylsulfonyl Acyl.

Preferably, the number of carbon atoms in the alkyl group is 1-8.

Preferably, the cation of the fluorosulfonyl radical reagent is any one of the compounds shown in formula 1 to formula 9:

The R ¹ and R ² are independently hydrogen or alkyl, R ³ is alkyl, R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R 10 , R ¹¹ , R ¹² , ^{R 13} , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R 20 , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , ^{R 29 ,} R ³⁰ , R ³¹ and R ³² are independently hydrogen, alkyl or electron deficient group.

Preferably, the fluorosulfonyl radical reagent is

The present invention provides a preparation method of the fluorosulfonyl free radical reagent described in the above technical scheme, comprising the following steps:

When the anion is

When, the preparation method comprises the following steps:

mixing the first raw material, sulfuryl fluoride, an alkaline reagent and an organic solvent, and performing a nucleophilic substitution reaction to obtain a first intermediate product;

mixing the first intermediate product, the second raw material and an organic solvent to perform a first electrophilic reaction to obtain a fluorosulfonyl radical reagent;

The first raw material has a structure shown in formula II-1 or formula II-2, and the first intermediate product has a structure shown in formula III-1 or formula III-2:

The second raw material is R ³ OTf, R ³ OSO ₂ F or R ³ HSO ₄ ;

When the anion is ^-BF ₄ , ^-BF ₆ , ^-PF ₆ , ^-PF ₄ , ^-SbF ₆ , ^-NTf ₂ or ^-AsF ₆ , the preparation method includes the following steps:

Mixing the first intermediate product, methyl iodide and an organic solvent, and performing a second electrophilic reaction to obtain a second intermediate product;

mixing the second intermediate product and the third raw material with an organic solvent, and performing an anion exchange reaction to obtain a fluorosulfonyl radical reagent;

The third raw material is AgBF ₄ , AgBF ₆ , AgPF ₆ , AgPF ₄ , AgSbF ₆ , AgNTf ₂ or AgAsF ₆ .

Preferably, the alkaline reagent includes an inorganic base reagent or an organic base reagent, and the inorganic base includes sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, potassium phosphate, One or more of potassium tert-butoxide, sodium methoxide, sodium ethoxide and sodium hydride; the organic base includes one or more of triethylamine, N,N-diisopropylethylamine, pyrrole and pyridine kind;

Preferably, the molar ratio of the first raw material, sulfuryl fluoride and alkaline reagent is 6:(7-7.5):(7-16).

Preferably, the organic solvent added during the nucleophilic substitution reaction includes acetonitrile, dichloromethane, ethyl acetate, benzene, toluene, acetone, 1,4-dioxane, ether, tetrahydrofuran, 1,2-bis One or more of ethyl chloride, dimethyl sulfoxide, N,N-dimethylformamide, N-methylpyrrolidone, methyl tert-butyl ether and chloroform.

Preferably, the molar ratio of the first intermediate product to the second raw material is 1:(1.1-2.0).

Preferably, the organic solvents acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide added during the first electrophilic reaction One or more of , methyl tert-butyl ether and chloroform.

Preferably, the temperature of the nucleophilic substitution reaction is -50-100°C, and the time is 1-48h; the temperature of the first electrophilic reaction is -50-100°C, and the time is 1-48h.

Preferably, the molar ratio of the first intermediate product to methyl iodide is 1:(1.05-5.0).

Preferably, the organic solvent added during the second electrophilic reaction includes tetrahydrofuran or acetonitrile.

Preferably, the molar ratio of the second intermediate product to the third raw material is 1:(1.05-5.0).

Preferably, the organic solvent added during the anion exchange reaction includes tetrahydrofuran or acetonitrile.

Preferably, the temperature of the second electrophilic reaction is -50-200°C, and the time is 1-48h; the temperature of the anion exchange reaction is -50-100°C, and the time is 1-48h.

The present invention provides the application of the fluorosulfonyl radical reagent described in the above technical scheme in the fluorosulfonyl radical reaction.

Preferably, the application includes the following steps:

The reaction substrate, fluorosulfonyl radical reagent, photosensitizer and organic solvent are mixed, and the fluorosulfonyl radical reaction is carried out under the irradiation conditions of ultraviolet light, blue light or visible light to obtain a fluorosulfonylated product; the reaction substrate includes alkenes or alkynes.

Preferably, the olefin compound has formula IV-1, formula IV-2, formula IV-3, formula IV-4, formula IV-5, formula IV-6, formula IV-7, formula IV-8 or formula IV The structure shown in -9:

In the formula IV-1, _R includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and in the substituted phenyl, substituted naphthyl and substituted biphenyl The substituent independently includes an alkyl group, an electron-rich group or an electron-poor group, and the electron-rich group is methoxy, ethoxy, propoxy, butoxy, dimethylamino, diethylamino, methyl Thio or ethylthio;

In the formula IV-2, R ₂ includes phenyl, substituted phenyl, ester group or carbonyl, R ₃ includes hydrogen, phenyl or substituted phenyl, R ₄ includes hydrogen, alkyl, phenyl or substituted phenyl; The substituent in the substituted phenyl group includes an alkyl group, an electron-rich group or an electron-deficient group;

In the formula IV-3, R includes hydrogen or alkyl, Ar includes phenyl, naphthyl, biphenyl, _substituted phenyl, substituted naphthyl or substituted biphenyl, and the substituted phenyl, substituted naphthyl and the substituents in the substituted biphenyl independently include an alkyl group, an electron-rich group or an electron-deficient group;

In the formula IV-4, R ₆ includes hydrogen, alkyl, phenyl or acyl, and n is 1 or 2;

In the formula IV-5, X is O or S, and R ₇ includes hydrogen, alkyl, phenyl or acyl;

In the formula IV-6, R and R _{independently} include alkyl, phenyl, naphthyl, biphenyl, _substituted phenyl, substituted naphthyl, substituted biphenyl or acyl, and the substituted phenyl, The substituents in the substituted naphthyl and the substituted biphenyl independently include an alkyl group, an electron-rich group or an electron-deficient group;

In the formula IV-7, m is 1-4;

In the formula IV-8, Ar includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and the substitution in the substituted phenyl, substituted naphthyl and substituted biphenyl The groups independently include alkyl groups, electron rich groups or electron deficient groups;

In the formula IV-9, p is 1-4, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ independently include hydrogen, alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl Or a substituted biphenyl group, the substituents in the substituted phenyl group, substituted naphthyl group and substituted biphenyl group independently include an alkyl group, an electron-rich group or an electron-deficient group.

Preferably, the photosensitizer includes a metal complex photocatalyst or an organic photocatalyst.

Preferably, the molar ratio of the reaction substrate to the fluorosulfonyl radical reagent is 0.1: (0.15-0.4).

Preferably, the molar ratio of the reaction substrate to the photosensitizer is 0.1:(0.001-0.01).

Preferably, the fluorosulfonyl radical reaction is carried out in the presence of an inorganic alkaline reagent.

Preferably, the inorganic alkaline reagent includes one or more of potassium carbonate, sodium carbonate, potassium phosphate and sodium bicarbonate.

Preferably, the molar ratio of the reaction substrate to the inorganic alkali reagent is 0.1: (0.1-0.3).

Preferably, the temperature of the fluorosulfonyl radical reaction is -60-100° C., and the time is 1-72 h.

The present invention provides a fluorosulfonyl radical reagent, which includes a cation and an anion, and the cation has the structure shown in formula I-1 or formula I-2. The fluorosulfonyl free radical reagent provided by the present invention can efficiently generate fluorosulfonyl free radicals and undergo corresponding free radical reactions, and the product yield is high; and the substrate adaptability of the fluorosulfonyl free radical reagent provided by the present invention is extremely wide, It can react with various types of olefin substrates and alkyne substrates to efficiently synthesize fluorosulfonylated products; at the same time, the fluorosulfonyl free radical reagent provided by the invention is a stable solid state at room temperature, non-volatile, and toxic Small, easy to store, easy to use, has important academic and application value.

In addition, the invention provides a preparation method of the fluorosulfonyl radical reagent, which is simple to operate and suitable for large-scale production.

Instructions attached

Fig. 1 is the ¹ H NMR figure of 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate prepared in Example 2;

Fig. 2 is the ¹⁹ F NMR chart of 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate prepared in Example 2;

Fig. 3 is the ¹³ C NMR chart of 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate prepared in Example 2;

Figure 4 is ^{the 1} H NMR figure of 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate prepared in Example 3 ;

Figure 5 is the ¹⁹ F NMR chart of 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate prepared in Example 3 ;

Figure 6 is the ¹³ C NMR figure of 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate prepared in Example 3 .

Detailed ways

The present invention provides a fluorosulfonyl radical reagent, including a cation and an anion, and the cation has a structure shown in formula I-1 or formula I-2:

The R ¹ and R ² are independently hydrogen or an alkyl group, R ³ is an alkyl group, Ar ¹ and Ar ² are independently an aromatic ring or a substituted aromatic ring;

The anion is

^- BF ₄ , ^- BF ₆ , ^- PF ₆ , ^- PF ₄ , ^- SbF ₆ , ^- NTf ₂ or ^- AsF ₆ .

In the present invention, the aromatic ring is preferably a benzene ring, a naphthalene ring, an anthracene ring or a phenanthrene ring, and the substituent in the substituted aromatic ring is preferably an alkyl group or an electron-deficient group. In the present invention, the electron deficient group preferably includes -F, -Cl, -Br, trifluoromethyl, nitrile, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl or Alkylsulfonyl.

In the present invention, the alkyl group can be a straight-chain alkyl group, or a branched-chain alkyl group or a cycloalkyl group; in the present invention, the number of carbon atoms in the alkyl group is preferably 1 to 8, more preferably 1 to 3, specifically methyl.

In the present invention, the cation of the fluorosulfonyl radical reagent is specifically any one of the compounds shown in formula 1 to formula 9:

The R ¹ and R ² are independently hydrogen or alkyl, R ³ is alkyl, R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ^{20 , R 21 ,} R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , R ²⁹ , R ³⁰ , R ³¹ and R ³² are independently hydrogen, alkyl or electron deficient group. In the present invention, the optional ranges of the alkyl group and the electron-deficient group are the same as those in the above technical solution, and will not be repeated here.

In the present invention, the fluorosulfonyl free radical reagent can specifically be

The present invention provides a preparation method of the fluorosulfonyl radical reagent described in the above technical solution. The present invention is based on the targeted selection of the anion species in the fluorosulfonyl free radical reagent. The preparation method is specifically described below.

In the present invention, unless otherwise specified, the raw materials used are commercially available products well known to those skilled in the art.

In the present invention, when the anion is

When, the preparation method of described fluorosulfonyl radical reagent comprises the following steps:

mixing the first raw material, sulfuryl fluoride, an alkaline reagent and an organic solvent, and performing a nucleophilic substitution reaction to obtain a first intermediate product;

mixing the first intermediate product, the second raw material and an organic solvent to perform a first electrophilic reaction to obtain a fluorosulfonyl radical reagent;

The first raw material has a structure shown in formula II-1 or formula II-2, and the first intermediate product has a structure shown in formula III-1 or formula III-2:

The second raw material is R ³ OTf, R ³ OSO ₂ F or R ³ HSO ₄ .

The invention mixes the first raw material, sulfuryl fluoride, alkaline reagent and organic solvent to carry out nucleophilic substitution reaction to obtain the first intermediate product. In the present invention, the alkaline reagent preferably includes an inorganic alkaline reagent or an organic alkaline reagent, and the inorganic base preferably includes sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate , potassium phosphate, potassium tert-butoxide, sodium methoxide, sodium ethoxide and sodium hydride, more preferably sodium hydride; the organic base preferably includes triethylamine, N,N-diisopropylethyl One or more of amine, pyrrole and pyridine, more preferably triethylamine. In the present invention, the organic solvent preferably includes acetonitrile, dichloromethane, ethyl acetate, benzene, toluene, acetone, 1,4-dioxane, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, di One or more of methyl sulfoxide, N,N-dimethylformamide, N-methylpyrrolidone, methyl tert-butyl ether and chloroform, more preferably acetonitrile or N,N-dimethylformamide amides. In the present invention, the molar ratio of the first raw material, sulfuryl fluoride and alkaline reagent is preferably 6:(7-7.5):(7-16), more preferably 6:7.3:(7.2-15); In the present invention, the amount of the organic solvent used is not particularly limited, as long as the nucleophilic substitution reaction proceeds smoothly.

In the present invention, the first raw material, sulfuryl fluoride, basic reagent and organic solvent are mixed, preferably the first raw material, basic reagent and organic solvent are mixed, and then passed through the mixed system under negative pressure. Sulfuryl fluoride gas is introduced; in the embodiment of the present invention, specifically, the mixed system is pumped to a negative pressure by a water pump, and then sulfuryl fluoride gas is introduced with a balloon.

In the present invention, the temperature of the nucleophilic substitution reaction is preferably -50 to 100°C, more preferably 20 to 50°C. Specifically, the nucleophilic substitution reaction can be carried out at room temperature, that is, no additional heating or Cooling; in the embodiment of the present invention, the room temperature is specifically 25°C. In the present invention, the time for the nucleophilic substitution reaction is preferably 1-48 hours, more preferably 5-30 hours, and even more preferably 10-12 hours. In the present invention, the nucleophilic substitution reaction is preferably carried out under stirring conditions. The present invention has no special limitation on the stirring conditions, and the stirring rate well known to those skilled in the art can be used.

In an embodiment of the present invention, when triethylamine is used as the basic reagent, specifically, at room temperature, the first raw material, the basic reagent and the organic solvent are mixed, and the mixed system is pumped to negative pressure. Use a balloon to introduce sulfuryl fluoride gas, and carry out nucleophilic substitution reaction under stirring at room temperature; when sodium hydride is used as an alkaline reagent, it is specifically added to a mixed solution of the first raw material and an organic solvent under the condition of an ice bath (0°C). Add sodium hydride in batches, keep warm and stir for 25 to 35 minutes, then warm up to room temperature, and stir at room temperature for 50 to 70 minutes, pump the resulting mixed system to negative pressure, then use a balloon to introduce sulfuryl fluoride gas, and carry out stirring at room temperature. nucleophilic substitution reaction.

The present invention preferably monitors the reaction process by TLC; after the reaction is completed, the present invention preferably quenches the resulting reaction solution with saturated ammonium chloride solution, extracts with dichloromethane, and washes with saturated brine after the organic phases are combined, and then passes through anhydrous sulfuric acid sodium drying, filtering, and the filtrate was concentrated to dryness by rotary evaporation, and the obtained residue was a crude product containing the first intermediate product, which was directly followed by the first electrophilic reaction; or the filtrate was concentrated to dryness by rotary evaporation, and the obtained The residue is separated by column chromatography to obtain the first intermediate product; the reagents used in the column chromatography separation are petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is preferably 20:1.

After the first intermediate product is obtained, the present invention mixes the first intermediate product, the second raw material and an organic solvent to perform a first electrophilic reaction to obtain a fluorosulfonyl free radical reagent. In the present invention, the organic solvent preferably includes acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, methyl tert-butyl One or more of base ether and chloroform, more preferably dichloromethane. In the present invention, the molar ratio of the first intermediate product to the second raw material is preferably 1: (1.1-2.0), and the present invention has no special limitation on the amount of the organic solvent, so as to ensure the smooth progress of the first electrophilic reaction. Can.

In the present invention, the first intermediate product and the second raw material are mixed with an organic solvent, specifically in a protective atmosphere, the first intermediate product is mixed with an organic solvent (or the mixed material liquid containing the first intermediate product is mixed with an organic solvent) solvent mixing), under ice bath (0°C) and stirring conditions, dropwise add the second raw material to the obtained mixed system; in the embodiment of the present invention, specifically, use a syringe to add the second raw material dropwise to the mixed system , the rate of the dropwise addition is preferably 4-5 mL/min, more preferably 4.5 mL/min.

In the present invention, the temperature of the first electrophilic reaction is preferably -50 to 100°C, more preferably -20 to 50°C. Specifically, the first electrophilic reaction can be carried out at room temperature; specifically, the second raw material drop After the addition, the ice in the ice bath melted naturally and returned to room temperature for the first electrophilic reaction. In the present invention, the time for the first electrophilic reaction is preferably 1-48 hours, more preferably 3-20 hours, and even more preferably 6-8 hours.

The present invention preferably monitors the first electrophilic reaction process by LC-MS; after the reaction is completed, the present invention preferably concentrates the obtained reaction solution through rotary evaporation, adds methyl tert-butyl ether to the obtained residue, stirs to separate out solids, and The supernatant was poured out, and the obtained solid was washed with methyl tert-butyl ether, and the target product fluorosulfonyl radical reagent was obtained after removing the solvent; remove.

In the present invention, when the anion is ^-BF ₄ , ^-BF ₆ , ^-PF ₆ , ^-PF ₄ , ^-SbF ₆ ^, -NTf ₂ or ^-AsF ₆ , the preparation method of the fluorosulfonyl radical reagent Include the following steps:

Mixing the first intermediate product, methyl iodide, reagent A and reagent B, and performing a second electrophilic reaction to obtain a second intermediate product;

Mixing the second intermediate product, the third raw material, reagent C and reagent D, and performing an anion exchange reaction to obtain a fluorosulfonyl radical reagent;

The third raw material is AgBF ₄ , AgBF ₆ , AgPF ₆ , AgPF ₄ , AgSbF ₆ , AgNTf ₂ or AgAsF ₆ .

In the present invention, the first intermediate product is the first intermediate product described in the above technical solution, which will not be repeated here.

The invention mixes the first intermediate product, methyl iodide and an organic solvent to carry out the second electrophilic reaction to obtain the second intermediate product. In the present invention, the molar ratio of the first intermediate product to methyl iodide is preferably 1:(1.05-5.0), more preferably 1:(2.5-3.5). In the present invention, the organic solvent preferably includes tetrahydrofuran or acetonitrile. In the present invention, there is no special limitation on the amount of the organic solvent, as long as the second electrophilic reaction can proceed smoothly. The method of mixing the first intermediate product, methyl iodide and organic solvent is not particularly limited in the present invention, as long as each component can be mixed evenly.

In the present invention, the temperature of the second electrophilic reaction is preferably -50 to 200°C, more preferably 0 to 100°C, further preferably 20 to 50°C; the time is preferably 1 to 48h, more preferably 12 to 24h, more preferably 15-20h.

After the second electrophilic reaction, the present invention preferably concentrates the obtained product system through rotary evaporation, and then drains the solvent through an oil pump to obtain the second intermediate product.

After the second intermediate product is obtained, the present invention mixes the second intermediate product, the third raw material and an organic solvent to perform anion exchange reaction to obtain a fluorosulfonyl free radical reagent. In the present invention, the molar ratio of the second intermediate product to the third raw material is preferably 1:(1.05-5.0), more preferably 1:(2.5-3.5). In the present invention, the organic solvent preferably includes tetrahydrofuran or acetonitrile. In the present invention, there is no special limitation on the amount of the organic solvent, as long as the second electrophilic reaction can proceed smoothly. The method of mixing the second intermediate product, the third raw material and the organic solvent is not particularly limited in the present invention, as long as each component can be mixed evenly.

In the present invention, the temperature of the anion exchange reaction is preferably -50 to 100°C, more preferably -30 to 80°C, further preferably -5 to 30°C; the time is preferably 1 to 48 hours, more preferably 4 to 12h, more preferably 6-10h.

After the anion exchange reaction, the present invention preferably concentrates the obtained product system by rotary evaporation, adds diethyl ether to the obtained residue, stirs to precipitate a solid, pours out the supernatant, washes the obtained solid with diethyl ether, and removes the solvent to obtain the target The product is a fluorosulfonyl free radical reagent; in the embodiments of the present invention, an oil pump is used to drain the solvent, so as to realize the removal of the solvent.

The present invention provides the application of the fluorosulfonyl radical reagent described in the above technical scheme in the fluorosulfonyl radical reaction. In the present invention, the application preferably includes the following steps:

The reaction substrate, fluorosulfonyl radical reagent, photosensitizer and organic solvent are mixed, and the fluorosulfonyl radical reaction is carried out under the irradiation conditions of ultraviolet light, blue light or visible light to obtain a fluorosulfonylated product; the reaction substrate includes alkenes or alkynes.

In the present invention, the olefin compound preferably has formula IV-1, formula IV-2, formula IV-3, formula IV-4, formula IV-5, formula IV-6, formula IV-7, formula IV-8 Or the structure shown in formula IV-9:

In the formula IV-1, _R preferably includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and in the substituted phenyl, substituted naphthyl and substituted biphenyl The substituents preferably independently include alkyl groups, electron-rich groups or electron-poor groups, and the electron-rich groups are preferably methoxy, ethoxy, propoxy, butoxy, dimethylamino, diethyl Amino group, methylthio group or ethylthio group, the optional range of the alkyl group and the electron-deficient group is preferably consistent with the above-mentioned technical solution, and will not be repeated here;

In the formula IV-2, _R2 preferably includes phenyl, substituted phenyl, ester group or carbonyl, _R3 preferably includes hydrogen, phenyl or substituted phenyl, _R4 preferably includes hydrogen, alkyl, phenyl or substituted Phenyl; the substituent in the substituted phenyl group preferably includes an alkyl group, an electron-rich group or an electron-deficient group, and the optional range of the alkyl group, an electron-rich group and an electron-deficient group is preferably the same as the above-mentioned technical scheme are consistent, and will not be repeated here;

In the formula IV-3, R _preferably includes hydrogen or alkyl, Ar preferably includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, the substituted phenyl, substituted The substituents in naphthyl and substituted biphenyl preferably independently include alkyl groups, electron-rich groups or electron-deficient groups, and the optional ranges of the alkyl groups, electron-rich groups and electron-deficient groups are preferably the same as those of the above-mentioned technology The scheme is consistent and will not be repeated here;

In the formula IV-4, R ₆ preferably includes hydrogen, alkyl, phenyl or acyl, and n is preferably 1 or 2;

In the formula IV-5, X is preferably O or S, _{and R7} preferably includes hydrogen, alkyl, phenyl or acyl; the optional range of the alkyl group is preferably consistent with the above-mentioned technical scheme, and specifically can be a straight chain Alkyl or cycloalkyl, preferably cyclohexane;

In the formula IV-6, R ₈ and R ₉ preferably independently include alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl, substituted biphenyl or acyl, and the substituted phenyl The substituents in , substituted naphthyl and substituted biphenyl preferably independently include an alkyl group, an electron-rich group or an electron-deficient group, and the optional ranges of the alkyl group, the electron-rich group and the electron-deficient group are preferably the same as Consistent in the above-mentioned technical scheme, no longer repeat them here;

In the formula IV-7, m is preferably 1-4;

In the formula IV-8, Ar preferably includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and in the substituted phenyl, substituted naphthyl and substituted biphenyl The substituent preferably independently includes an alkyl group, an electron-rich group or an electron-deficient group, and the optional range of the alkyl group, an electron-rich group and an electron-deficient group is preferably consistent with the above-mentioned technical solution, and will not be repeated here. ;

In the formula IV-9, p is preferably 1-4, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ preferably independently include hydrogen, alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted Naphthyl or substituted biphenyl, the substituents in the substituted phenyl, substituted naphthyl and substituted biphenyl preferably independently include alkyl, electron-rich groups or electron-poor groups, the alkyl, electron-rich The optional ranges of groups and electron-deficient groups are preferably consistent with those in the above-mentioned technical solution, and will not be repeated here.

In the present invention, the molar ratio of the reaction substrate to the fluorosulfonyl radical reagent is preferably 0.1:(0.15-0.4), more preferably 1:(0.2-0.3). In the present invention, the photosensitizer preferably includes a metal complex photocatalyst or an organic photocatalyst; the metal complex photocatalyst preferably includes an Ir complex, a Ru complex or a Cu complex, and the Ir complex is preferably Ir (ppy) ₃ ; the organic photocatalyst preferably includes PTH, EosinY or 4CzIPN. In the present invention, the molar ratio of the reaction substrate to the photosensitizer is preferably 0.1:(0.001-0.01). In the present invention, the organic solvent preferably includes 1,4-dioxane, tetrahydrofuran or diethyl ether; in the present invention, there is no special limitation on the amount of the organic solvent, as long as the fluorosulfonyl radical reaction proceeds smoothly. In the present invention, the fluorosulfonyl radical reaction can be carried out in the presence or absence of an inorganic alkali reagent. Specifically, the fluorosulfonyl radical reaction is preferably carried out in the presence of an inorganic alkali Carry out under reagent existence condition, described inorganic base reagent preferably comprises one or more in potassium carbonate, sodium carbonate, potassium phosphate and sodium bicarbonate; The mol ratio of described reaction substrate and inorganic base reagent is preferably 0.1:( 0.1～0.3); The effect of described inorganic alkaline reagent is to neutralize the acid produced in the reaction.

In the present invention, there is no special limitation on the mixing method of the reaction substrate, fluorosulfonyl radical reagent, photosensitizer and organic solvent, as long as each component is uniformly mixed. In the present invention, the temperature of the fluorosulfonyl radical reaction is preferably -60 to 100°C, more preferably 15 to 40°C. Specifically, the fluorosulfonyl radical reaction can be carried out at room temperature; the fluorine The time for the sulfonyl radical reaction is preferably 1-72 h, more preferably 6-18 h. In the present invention, the fluorosulfonyl radical reaction is preferably carried out under a protective atmosphere and stirring conditions, and the protective gas providing the protective atmosphere is preferably argon, and the present invention has no special limitation on the rate of stirring. Stirring rates known to those skilled in the art will suffice. The present invention has no special limitation on the light source that provides ultraviolet light, blue light or visible light, and the light source well known to those skilled in the art can be used; in the embodiment of the present invention, specifically, the fluorosulfonyl radical In response, the light source that provides blue light is preferably a blue LED light.

After the fluorosulfonyl radical reaction, the present invention preferably removes the solvent in the resulting reaction solution, and separates the obtained crude product by silica gel column chromatography to obtain the fluorosulfonylated product. In the present invention, the solvent in the reaction solution is removed The method is preferably vacuum distillation. In the present invention, the developing agent used in the silica gel column chromatography separation is preferably petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether and ethyl acetate is preferably 40:1; the silica gel column chromatography separation adopts The silica gel particle size is preferably 200-300 mesh.

The technical solutions in the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Apparently, the described embodiments are only some of the embodiments of the present invention, but not all of them. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

Example 1

To prepare 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate, the reaction formula is as follows:

At room temperature (25°C), mix triethylamine (1500mmol), acetonitrile (600mL) and 2-phenylimidazole (600mmol), pump the resulting mixture to negative pressure, and introduce sulfuryl fluoride gas with a balloon (730mmol), stirred at room temperature and reacted for 12h, and TLC monitored the completion of the reaction; the reaction solution was quenched with saturated ammonium chloride solution, extracted with dichloromethane (300mL×3 times), and the organic phases were combined and washed with saturated brine (600mL). Then dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to dryness by a rotary evaporator, and the obtained residue was a crude product containing 2-phenyl-1H-imidazole-1-sulfonyl fluoride;

Under nitrogen protection, dichloromethane (600 mL) was added to the crude product containing 2-phenyl-1H-imidazole-1-sulfonyl fluoride, cooled in an ice bath to 0° C. Methyl trifluoromethanesulfonate (592mmol) was added dropwise at a rate of 4.5mL/min, the ice in the ice bath melted naturally and returned to room temperature, reacted at room temperature for 4h, and LC-MS monitored the completion of the reaction; the reaction solution was rotary evaporated Concentrate to dryness, add methyl tert-butyl ether (500mL) to the resulting residue, stir to precipitate a solid, pour off the supernatant, and wash the obtained solid with methyl tert-butyl ether (500mL×2), then use The solvent was drained by an oil pump, and the obtained white solid was 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate, and the total yield of the two-step reaction was 91%.

Example 2

To prepare 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate, the reaction formula is as follows:

In an ice bath (0°C), NaH (720mmol) was added in batches to a solution of 2-phenylbenzimidazole (600mmol) in DMF (600mL), stirred at 0°C for 30min and then raised to room temperature. Stir at low temperature for 1 h, pump the resulting mixed system to negative pressure, introduce sulfuryl fluoride gas (730 mmol) with a balloon, stir and react at room temperature for 12 h, and monitor the completion of the reaction by TLC; the reaction solution is quenched with water, extracted with ethyl acetate (400 mL× 3 times), the organic phases were combined and washed with saturated brine (600mL), then dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated by a rotary evaporator, and the residue was separated by column chromatography (by volume ratio, the reagent used Petroleum ether: ethyl acetate = 20:1), to obtain 2-phenyl-1H-benzimidazole-1-sulfonyl fluoride;

Under the condition of nitrogen protection, the 2-phenyl-1H-benzimidazole-1-sulfonyl fluoride was mixed with dichloromethane (600mL), cooled to 0°C in an ice bath, and 4.5mL Methyl trifluoromethanesulfonate (592mmol) was added dropwise at a rate of 1/min, the ice in the ice bath melted naturally and returned to room temperature, reacted at room temperature for 4h, and LC-MS monitored the completion of the reaction; the reaction solution was concentrated by a rotary evaporator To dryness, add methyl tert-butyl ether (500mL) to the resulting residue, stir to precipitate a solid, pour off the supernatant, and wash the obtained solid with methyl tert-butyl ether (500mL×2), then use an oil pump to pump The solvent was dried, and the obtained white solid was 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-benzimidazole trifluoromethanesulfonate, and the overall yield of the two-step reaction was 86%.

Example 3

To prepare 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole triflate, the reaction formula is as follows:

Prepare 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate according to the method of Example 15, except that In Example 15, "2-phenylbenzimidazole" was replaced with "2-(4-trifluoromethylphenyl)benzimidazole"; the final white solid obtained was 1-(fluorosulfonyl)-3-methyl -2-(4-Trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate, the total yield was 82%.

Application example 1

Prepare 2-phenylethylene-1-sulfonyl fluoride, the structural formula is as follows:

In a 20 mL Schlenk sealed tube, add 0.1 mmol styrene, 0.2 mmol fluorosulfonyl free radical reagent (specifically 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethyl) prepared in Example 16 phenyl)-1H-benzimidazole trifluoromethanesulfonate), 0.001mmol Ir(ppy) ₃ and a magnetic stirrer, under the protection of argon, add 4mL of dry dioxane, and irradiate with a blue LED lamp 1. Under room temperature conditions, the reaction was stirred for 12 hours, and the reaction was monitored by TLC; the resulting reaction solution was distilled under reduced pressure to remove the solvent to obtain a crude product, and the crude product was carried out to silica gel column chromatography (by volume, the developing agent was petroleum Ether:ethyl acetate=40:1; silica gel particle size is 200-300 mesh), to obtain 2-phenylethylene-1-sulfonyl fluoride with a yield of 94% (E/Z=92:8).

In order to understand the reaction mechanism, follow the above method, the difference is that the free radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO, 0.2mmol) is added to the reaction system , followed by a fluorosulfonyl radical reaction, the results showed that no fluorosulfonylated products were observed. This shows that the reaction pathway for preparing 2-phenylethylene-1-sulfonyl fluoride is a free radical process, and further shows that the reagent provided by the present invention acts as a fluorosulfonyl free radical donor in the reaction.

Application example 2

According to the method of application example 1, the difference is that the fluorosulfonyl radical reagent used in this application example is 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H- Imidazole trifluoromethanesulfonate, the final yield of 2-phenylethylene-1-sulfonyl fluoride was 72% (E/Z=76:24).

Comparative example 1～3

According to the method of Application Example 1, the difference is that the fluorosulfonyl radical reagents used in Comparative Examples 1 to 3 are Compound 2b, Compound 2c and Compound 2e respectively, and the specific structures and involved reaction formulas are as follows:

The product yield data in Application Examples 1-2 and Comparative Examples 1-3 are shown in Table 1. It can be seen from Table 1 that the yield of the product is higher when the fluorosulfonyl radical reagent provided by the present invention is used for the fluorosulfonyl radical reaction.

Product yield data in table 1 application example 1～2 and comparative example 1～3

the	Fluorosulfonyl free radical reagent	Product yield (%)	Product E/Z configuration ratio
Application example 1	Compound 2a	94	92:8
Application example 2	Compound 2d	72	76:24
Comparative example 1	Compound 2b	0	-
Comparative example 2	Compound 2c	Trace	-
Comparative example 3	Compound 2e	8	75:25

Application example 3

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by R ₁ -CH=CH ₂ , and the amount of fluorosulfonyl radical reagent is 0.2 mmol or 0.3 mmol, the substrate structure, fluorine The structure and yield of the sulfonylated product are shown in Table 2, and the general reaction formula is as follows:

Substrate structure, product structure and yield data in table 2 application example 3

Note: a in Table 2 indicates that the amount of fluorosulfonyl radical reagent used in the preparation process is 0.2 mmol, and b indicates that the amount of fluorosulfonyl free radical reagent used in the preparation process is 0.3 mmol.

Application example 4

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by ArR ₅ -C=CH ₂ , and the amount of fluorosulfonyl radical reagent used in the preparation process is 0.3 mmol, the substrate structure, fluorine The structure and yield of the sulfonylated product (corresponding to 3ba) are shown in Table 3, and the general reaction formula is as follows:

Application example 5

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by

In addition, the amount of fluorosulfonyl radical reagent used in the preparation process was 0.3 mmol. The structure of the substrate, the structure of the fluorosulfonylated products (corresponding to 3bb and 3bc) and the yield are shown in Table 3. The general reaction formula is as follows:

Application example 6

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by R ₂ R ₃ -C=CR ₄ H, and the amount of fluorosulfonyl radical reagent used in the preparation process is 0.3 mmol, the substrate The structure, fluorosulfonylation product structure (corresponding to 3bd～3bs) and yield are shown in Table 3. The general reaction formula is as follows:

Substrate structure, product structure and yield data in Table 3 Application Examples 4-6

Note: For the data of "yield" in Table 3, the yield in brackets is the yield data when 0.3mmol of FSO ₂ Cl is used to prepare fluorosulfonylated products, and the yield outside the brackets is the yield of fluorosulfonylation provided by the present invention using 0.3mmol Yield data for the preparation of fluorosulfonylated products by acyl radical reagents.

Application example 7

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by

And add 0.1mmol K ₂ CO ₃ ; the substrate structure, fluorosulfonylation product (corresponding to 3ca and 3cb) structure and yield are shown in Table 4, and the general reaction formula is as follows:

Application example 8

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by

And add 0.1mmol K ₂ CO ₃ ; the structure of the substrate, the structure of the fluorosulfonylated product (corresponding to 3cc) and the yield are shown in Table 4. The general reaction formula is as follows:

Application example 9

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by

And add 0.1mmol K ₂ CO ₃ ; the structure of the substrate, the structure of the fluorosulfonylation product (corresponding to 3cd) and the yield are shown in Table 4. The general reaction formula is as follows:

Application Example 10

According to the method of application example 1, the difference is that the substrate in application example 1 is replaced by R ₇ X-CH=CH ₂ , and 0.1 mmol K ₂ CO ₃ is added; the structure of the substrate, the fluorosulfonylated product ( The structures and yields corresponding to 3ce～3cj) are shown in Table 4, and the general reaction formula is as follows:

Substrate structure, product structure and yield data in Table 4 Application Examples 7-10

It can be seen from the above application examples that the fluorosulfonyl free radical reagent provided by the present invention is applicable to a wide range of substrates, including substituted or unsubstituted phenyl olefins, naphthyl olefins, biphenyl olefins, cyclic phenyl olefins, disubstituted, Trisubstituted phenylalkenes (in particular, triphenylethylene also yields high yields), electron-deficient phenylalkenes, and various alkenyl ethers, alkenyl amines, and thioether alkenes substrates .

The above is only a preferred embodiment of the present invention, it should be pointed out that, for those of ordinary skill in the art, without departing from the principle of the present invention, some improvements and modifications can also be made, and these improvements and modifications can also be made. It should be regarded as the protection scope of the present invention.

Claims (28)

1. A fluorosulfonyl free radical reagent, characterized in that it includes a cation and an anion, and the cation has a structure shown in formula I-1 or formula I-2:

   

   The R ¹ and R ² are independently hydrogen or an alkyl group, R ³ is an alkyl group, Ar ¹ and Ar ² are independently an aromatic ring or a substituted aromatic ring;

   The anion is

   

   -BF ₄ , -BF ₆ , -PF ₆ , -PF ₄ , -SbF ₆ , -NTf ₂ or -AsF ₆ .
2. The fluorosulfonyl free radical reagent according to claim 1, wherein the aromatic ring is a benzene ring, a naphthalene ring, an anthracene ring or a phenanthrene ring, and the substituent in the substituted aromatic ring is an alkyl group or an electron-deficient group group.
3. The fluorosulfonyl free radical reagent according to claim 2, wherein the electron-deficient groups include -F, -Cl, -Br, trifluoromethyl, nitrile, nitro, ester, aldehyde , acetyl, fluorosulfonyl, phenylsulfonyl or alkylsulfonyl.
4. The fluorosulfonyl radical reagent according to claim 1, characterized in that the number of carbon atoms in the alkyl group is 1-8.
5. The fluorosulfonyl radical reagent according to any one of claims 1 to 4, wherein the cation of the fluorosulfonyl radical reagent is any one of the compounds shown in formula 1 to formula 9:

   

   

   The R ¹ and R ² are independently hydrogen or alkyl, R ³ is alkyl, R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R 10 , R ¹¹ , R ¹² , ^{R 13} , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ^{20 , R 21 ,} R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , R ²⁹ , R ³⁰ , R ³¹ and R ³² are independently hydrogen, alkyl or electron deficient group.
6. The fluorosulfonyl free radical reagent according to any one of claims 1 to 5, wherein the fluorosulfonyl free radical reagent is

   

   
7. The preparation method of the fluorosulfonyl radical reagent described in any one of claims 1 to 6, characterized in that when the anion is

   

   When, the preparation method comprises the following steps:

   mixing the first raw material, sulfuryl fluoride, an alkaline reagent and an organic solvent, and performing a nucleophilic substitution reaction to obtain a first intermediate product;

   mixing the first intermediate product, the second raw material and an organic solvent to perform a first electrophilic reaction to obtain a fluorosulfonyl radical reagent;

   The first raw material has a structure shown in formula II-1 or formula II-2, and the first intermediate product has a structure shown in formula III-1 or formula III-2:

   

   

   The second raw material is R ³ OTf, R ³ OSO ₂ F or R ³ HSO ₄ ;

   When the anion is -BF ₄ , -BF ₆ , -PF ₆ , -PF ₄ , -SbF ₆ , -NTf ₂ or -AsF ₆ , the preparation method includes the following steps:

   Mixing the first intermediate product, methyl iodide and an organic solvent, and performing a second electrophilic reaction to obtain a second intermediate product;

   mixing the second intermediate product and the third raw material with an organic solvent, and performing an anion exchange reaction to obtain a fluorosulfonyl radical reagent;

   The third raw material is AgBF ₄ , AgBF ₆ , AgPF ₆ , AgPF ₄ , AgSbF ₆ , AgNTf ₂ or AgAsF ₆ .
8. The preparation method according to claim 7, wherein the alkaline reagent comprises an inorganic base reagent or an organic base reagent, and the inorganic base comprises sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, One or more of sodium bicarbonate, potassium bicarbonate, potassium phosphate, potassium tert-butoxide, sodium methoxide, sodium ethoxide and sodium hydride; the organic base includes triethylamine, N,N-diisopropylethyl One or more of amine, pyrrole and pyridine;
9. The preparation method according to claim 7, characterized in that the molar ratio of the first raw material, sulfuryl fluoride and alkaline reagent is 6:(7-7.5):(7-16).
10. The preparation method according to claim 7, wherein the organic solvent added in the nucleophilic substitution reaction process includes acetonitrile, methylene chloride, ethyl acetate, benzene, toluene, acetone, 1,4-dioxane Cyclo, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, N-methylpyrrolidone, methyl tert-butyl ether and chloroform or Various.
11. The preparation method according to claim 7, characterized in that the molar ratio of the first intermediate product to the second raw material is 1:(1.1-2.0).
12. The preparation method according to claim 7, characterized in that, the organic solvents acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, dimethylmethylene added in the first electrophilic reaction process One or more of sulfone, N,N-dimethylformamide, methyl tert-butyl ether and chloroform.
13. The preparation method according to any one of claims 7 to 12, characterized in that, the temperature of the nucleophilic substitution reaction is -50 to 100° C., and the time is 1 to 48 h; the temperature of the first electrophilic reaction is -50～100℃, the time is 1～48h.
14. The preparation method according to claim 7, characterized in that the molar ratio of the first intermediate product to methyl iodide is 1:(1.05-5.0).
15. The preparation method according to claim 7, characterized in that, the organic solvent added during the second electrophilic reaction comprises tetrahydrofuran or acetonitrile.
16. The preparation method according to claim 7, characterized in that the molar ratio of the second intermediate product to the third raw material is 1:(1.05-5.0).
17. The preparation method according to claim 7, characterized in that, the organic solvent added during the anion exchange reaction comprises tetrahydrofuran or acetonitrile.
18. According to the preparation method described in claim 7, 14, 15, 16 or 17, it is characterized in that, the temperature of the second electrophilic reaction is -50～200°C, and the time is 1～48h; the anion exchange reaction The temperature is -50～100℃, and the time is 1～48h.
19. The application of the fluorosulfonyl free radical reagent described in any one of claims 1 to 6 in the fluorosulfonyl free radical reaction.
20. The application according to claim 19, characterized in that the application comprises the steps of:

    The reaction substrate, fluorosulfonyl radical reagent, photosensitizer and organic solvent are mixed, and the fluorosulfonyl radical reaction is carried out under the irradiation conditions of ultraviolet light, blue light or visible light to obtain a fluorosulfonylated product; the reaction substrate includes alkenes or alkynes.
21. The application according to claim 20, wherein the olefin compound has formula IV-1, formula IV-2, formula IV-3, formula IV-4, formula IV-5, formula IV-6, formula IV -7, the structure shown in formula IV-8 or formula IV-9:

    

    In the formula IV-1, _R includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and in the substituted phenyl, substituted naphthyl and substituted biphenyl The substituent independently includes an alkyl group, an electron-rich group or an electron-poor group, and the electron-rich group is methoxy, ethoxy, propoxy, butoxy, dimethylamino, diethylamino, methyl Thio or ethylthio;

    In the formula IV-2, R ₂ includes phenyl, substituted phenyl, ester group or carbonyl, R ₃ includes hydrogen, phenyl or substituted phenyl, R ₄ includes hydrogen, alkyl, phenyl or substituted phenyl; The substituent in the substituted phenyl group includes an alkyl group, an electron-rich group or an electron-deficient group;

    In the formula IV-3, R includes hydrogen or alkyl, Ar includes phenyl, naphthyl, biphenyl, _substituted phenyl, substituted naphthyl or substituted biphenyl, and the substituted phenyl, substituted naphthyl and the substituents in the substituted biphenyl independently include an alkyl group, an electron-rich group or an electron-deficient group;

    In the formula IV-4, R ₆ includes hydrogen, alkyl, phenyl or acyl, and n is 1 or 2;

    In the formula IV-5, X is O or S, and R ₇ includes hydrogen, alkyl, phenyl or acyl;

    In the formula IV-6, R and R _{independently} include alkyl, phenyl, naphthyl, biphenyl, _substituted phenyl, substituted naphthyl, substituted biphenyl or acyl, and the substituted phenyl, The substituents in the substituted naphthyl and the substituted biphenyl independently include an alkyl group, an electron-rich group or an electron-deficient group;

    In the formula IV-7, m is 1-4;

    In the formula IV-8, Ar includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and the substitution in the substituted phenyl, substituted naphthyl and substituted biphenyl The groups independently include alkyl groups, electron rich groups or electron deficient groups;

    In the formula IV-9, p is 1-4, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ independently include hydrogen, alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl Or a substituted biphenyl group, the substituents in the substituted phenyl group, substituted naphthyl group and substituted biphenyl group independently include an alkyl group, an electron-rich group or an electron-deficient group.
22. The application according to claim 20, characterized in that the photosensitizer comprises a metal complex photocatalyst or an organic photocatalyst.
23. The use according to any one of claims 20 or 21, characterized in that the molar ratio of the reaction substrate to the fluorosulfonyl radical reagent is 0.1:(0.15-0.4).
24. The use according to claim 20 or 22, characterized in that the molar ratio of the reaction substrate to the photosensitizer is 0.1:(0.001-0.01).
25. The application according to claim 20, characterized in that the fluorosulfonyl radical reaction is carried out in the presence of an inorganic alkali reagent.
26. The application according to claim 25, wherein the inorganic alkali reagent comprises one or more of potassium carbonate, sodium carbonate, potassium phosphate and sodium bicarbonate.
27. The use according to claim 20, 21, 25 or 26, characterized in that the molar ratio of the reaction substrate to the inorganic alkali reagent is 0.1: (0.1-0.3).
28. The application according to claim 20, 21, 22, 25 or 26, characterized in that the temperature of the fluorosulfonyl radical reaction is -60-100°C, and the time is 1-72h.

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